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Neuroradiology |
1 From the Departments of Radiology (M.H.L., J.F., J.J.G., S.T.H., G.J.H., R.G.G.) and Neurology (W.J.K.), Massachusetts General Hospital, GRB285, 14 Fruit St, Boston, MA 02114-9657. From the 1998 RSNA scientific assembly. Received October 20, 1998; revision requested December 17; revision received March 23, 1999; accepted March 26. R.G.G. supported in part by National Institutes of Health grants NS 34626 and RR 1321 and by an educational grant from GE Medical Systems. M.H.L. supported in part by a 1996 RSNA Seed Grant. Address reprint requests to M.H.L. (e-mail: mlev@partners.org).
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Abstract |
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MATERIALS AND METHODS: Nonenhanced CT was performed in 21 patients with acute (<6 hours) middle cerebral arterial stroke and nine control patients. Two blinded neuroradiologists rated all scans for presence of parenchymal hypoattenuation. Images were reviewed at a picture archiving and communication system (PACS) workstation, with standard, locally determined center level and window width settings of 20 and 80 HU and with variable soft-copy settings initially centered at a level of 32 HU with a width of 8 HU. Reviewers altered settings to accentuate gray and white matter contrast.
RESULTS: With standard viewing parameters, sensitivity and specificity for stroke detection were 57% and 100%. Sensitivity increased to 71% with variable window width and center level settings, without loss of specificity. Receiver operating characteristic analysis revealed a significant improvement in accuracy with nonstandard, soft-copy review settings (P = .03, one-tailed z test).
CONCLUSION: In nonenhanced CT of the head, detection of ischemic brain parenchyma is facilitated by soft-copy review with variable window width and center level settings to accentuate the contrast between normal and edematous tissue.
Index terms: Brain, CT, 10.781, 174.12111 • Brain, infarction, 10.781, 174.781 • Brain, ischemia, 10.781, 174.781
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Introduction |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Given the recent markedly increased use of freestanding picture archiving and communication system (PACS) workstations by radiology departments, the potential for increasing diagnostic accuracy through interactive image interpretation, without increasing the time or expense required to print and review hard-copy images at multiple window width and center level settings, presently exists (9–11).
The advent of thrombolytic therapy for acute stroke makes CT-aided detection of areas of hypoattenuating ischemic parenchyma, as well as better characterization of its predictive value for hemorrhage after treatment, exceedingly important. Current guidelines (8,12–15) recommend that thrombolytic therapy be avoided if CT of the head performed without the administration of contrast material demonstrates early changes of recent major infarction or hemorrhage. The ability of physicians to detect parenchymal hypoattenuation, however, is limited (15–20). In the first European Cooperative Acute Stroke Study (ECASS), for example, more than half the protocol violations were due to failure to recognize early nonenhanced CT signs of infarction (13,19).
In animal models of middle cerebral arterial (MCA) stroke, the decrease in CT attenuation in ischemic tissue due to cytotoxic edema is less than 8 HU at 4 hours after ictus (21–25). It is therefore possible that image review by using narrow, variable, soft-copy window width and center level settings, chosen to accentuate this small difference between normal and ischemic gray and white matter attenuation, could increase the conspicuity of hypoattenuating tissue (Figs 1, 2). We performed this study to assess the use of nonstandard, variable window width and center level review settings at nonenhanced CT in the detection of MCA stroke.
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MATERIALS AND METHODS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The approximate 2:1 ratio of the number of study patients to the number of control patients was chosen to more closely simulate our typical clinical experience than would a 1:1 ratio. The 21 MCA study patients included 17 with large (greater than one-third of the MCA territory) inferior division, superior division, or proximal MCA infarctions, and four patients with only small basal ganglia infarctions. Only patients without substantial cerebral swelling (sulcal or ventricular effacement) were chosen; three patients had equivocal hyperattenuating MCAs relative to the contralateral normal MCA attenuation.
The mean ages of the MCA study patients and of the control patients were 68.2 years ± 15.4 (SD) (age range, 27–91 years) and 59.8 years ± 19.6 (age range, 23–73 years), respectively; the mean age of the entire patient pool was 66.8 years ± 16.4 (age range, 23–91 years). The control group consisted of six men and three women; the study group included 13 men and eight women. For the study patients, the mean time between onset of stroke ictus and imaging was 2 hours 14 minutes ± 1 hour 18 minutes (range, 25.5 minutes to 5 hours 48 minutes).
Routine nonenhanced CT scanning was performed with the patient's head in a headholder with a CT HiSpeed Advantage scanner (GE Medical Systems, Milwaukee, Wis) in the hospital emergency department by using the following nonhelical scanning technique: 120 kV, 170 mA, 2-second scanning time, and 5-mm section thickness. Coverage was from the skull base to the vertex by obtaining contiguous axial sections parallel to the jugum sphenoidale. All examinations were monitored by a neuroradiology staff member or fellow.
Retrospective image review was performed at a PACS workstation (Impax RS3000 1K review station; AGFA Technical Imaging Systems, Richfield Park, NJ) by two board-certified neuroradiologists (M.H.L., J.J.G.) experienced in the interpretation of stroke CT scans and blinded to the clinical history and lateralization of symptoms but aware of the suspicion of acute MCA-division embolic stroke. Patient name, age, sex, and scanning date were electronically masked during image review. Neither of the reviewers had participated in the selection of the patients.
Nonenhanced CT images were evaluated for evidence of focal, asymmetric, parenchymal areas of low attenuation, with special attention paid to MCA-territory gray matter and white matter interfaces. In the instructions given to the readers, a "hyperdense MCA sign" was not specifically included as a diagnostic criterion for MCA stroke. Readers were notified of the location of any prior (older than 3 weeks) strokes indicated on the scans and were instructed to exclude these from their readings.
Each of the nonenhanced CT scans was reviewed in random order at two separate readout sessions 4 weeks apart. All scans were independently rated by both readers according to the following 1–5 scale: "1" indicated definite absence of acute MCA stroke; "2" indicated probable absence of acute MCA stroke; "3" indicated possible acute MCA stroke; "4" indicated probable acute MCA stroke; and "5" indicated definite acute MCA stroke. After recording their individual ratings, the readers discussed the case and recorded a consensus rating.
Images were reviewed at each session by using two distinct sets of viewing parameters. During the first readout session, only standard, preset, virtual hard-copy window width and center level settings were used for image evaluation. During the follow-up readout session, nonstandard, interactive, variable soft-copy window width and center level settings were used in addition to the standard settings. The standard, virtual hard-copy settings were preset to an 80-HU window width and a 20-HU center level. The variable soft-copy settings consisted of two initial preset defaults of an 8-HU window width with a 32-HU center level and a 30-HU window width with a 35-HU center level, which were subsequently custom-adjusted as necessary (range, approximately 1–30-HU window width and 28–36-HU center level) during the readout to maximize gray matter and white matter contrast, which accentuated the subtle attenuation differences between normal and acutely edematous ischemic brain parenchyma.
The time required for image review was recorded for one reader only (J.J.G.). Mean time for the standard review versus the variable soft-copy review was compared by using the Student t test.
For each patient, the recorded ratings were correlated with the final discharge diagnosis of MCA stroke or no MCA stroke. Correlative modalities used to establish the final diagnosis included arteriography and follow-up CT, magnetic resonance (MR) imaging, and clinical findings that demonstrated a new MCA-territory infarction.
Sensitivities, specificities, and accuracies were computed both by defining ratings of 3 or higher as positive for stroke and according to stricter criteria by counting only ratings of 4 or 5 as positive for stroke.
Binormal receiver operating characteristic (ROC) curves of both the standard and variable soft-copy ratings were constructed for each reader and for the consensus readings. The areas under the respective ROC curves, a measure of diagnostic accuracy, were calculated and compared by using the computer software program CORROC2 (Metz CE, Shen JH, Kronman HB, Wang PL, Department of Radiology, University of Chicago, Ill, 1994), which is used to analyze categoric data (26,27). Statistical significance was established by using the univariate z-score test.
Interobserver agreement was measured by using the weighted 
statistic, which was calculated with SAS statistical package version 6.12 (SAS Institute, Cary, NC). values may range from -1 to 1; as suggested by Landis and Koch (28), a statistic of 0.40 or greater is considered a moderately strong association (16). Others (29) have noted that a statistic greater than 0.75 represents excellent interobserver agreement, a statistic of 0.40–0.75 represents fair to good interobserver agreement, and a statistic of less than 0.40 represents poor interobserver agreement.
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RESULTS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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The sensitivities, specificities, and accuracies of nonenhanced CT in the detection of acute MCA stroke for both individual and consensus readings are shown in Table 1. For the consensus readings, by using standard viewing parameters and defining a rating of 4 or 5 (probable or definite stroke) as positive for stroke, the sensitivity and specificity for stroke detection on the nonenhanced scans were 14% and 100%, respectively. The corresponding sensitivity and specificity increased to 57% and 100% when a rating of 3 (possible stroke) or higher was considered positive for stroke. When images were reviewed by using the variable window width and center level settings, sensitivity and specificity for stroke detection increased to 48% and 100% when a rating of 4 or 5 was considered positive for stroke and to 71% and 100% when a rating of 3 or higher was considered positive. Of interest, when a rating of 3 or higher was defined as positive for acute MCA stroke, both sensitivity and specificity were improved or unchanged for each reader and for the consensus readings.
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statistics were used to measure interreader variability. Analysis of the variability between readers 1 and 2 revealed a value of 0.48 for the standard window and level readings and a value of 0.50 for the variable soft-copy window and level readings; a statistic of at least 0.4 is considered to indicate a moderately strong association.
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DISCUSSION |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Sensitivity values for nonenhanced CT stroke detection reported in the literature vary. Because individuals in control groups without stroke have only infrequently been included as subjects in published reports, the specificity of CT scanning in stroke detection is less well established (34). In a 1989 study of 36 patients with MCA infarction, CT results within 4 hours of stroke onset were positive in 70% of patients (3). Current-generation CT scanners can probably depict stroke as sensitively and as early as conventional T2-weighted MR imagers (35,36).
It is important to note that ischemic changes on CT scans may be predictive of outcome, response to thrombolytic therapy, and regions likely to become infarcted (4,8,12,14,37). Because of the increased risk of fatal parenchymal hemorrhage in ECASS patients with hypoattenuating areas of greater than one-third the MCA territory or sulcal effacement on early nonenhanced CT scans, these findings are considered by some to be contraindications to thrombolytic treatment (8,12–15). In the National Institute of Neurological Disorders and Stroke, or NINDS, study, which showed a benefit from thrombolytic agents administered intravenously within 3 hours of stroke onset, there was a trend toward improved outcome despite initial CT-observed hypoattenuation (8). It is a more controversial point that in the ECASS, a positive effect of intravenous thrombolyis was revealed only after careful retrospective review of the initial CT scans with the application of strict exclusion criteria for hypoattenuation of greater than one-third of the MCA territory (14,19). This difference may be partly related to the longer 6-hour treatment window applied to the ECASS patients. Furthermore, based on additional review of the ECASS data, it has been suggested that the subgroup of patients with acute stroke without demonstrable ischemia on nonenhanced CT scans is also unlikely to benefit from intravenous thrombolysis (14). Thus, the accurate early identification of hypo-attenuating ischemic parenchyma is a priority in CT imaging in stroke patients.
The pathophysiology underlying the CT-observed changes found in acute stroke is discussed at length in a recent review by Marks (23). Early CT-depicted hypoattenuation reflects cytotoxic edema secondary to failure of ion pumps in response to inadequate supply of adenosine triphosphate, or ATP (38). The attenuation in Hounsfield units seen with CT scanning in patients with acute stroke is directly proportional to the degree of cytotoxic edema; an increase in tissue water content by 1% results in a 2.5-HU decrease in parenchymal attenuation, which corresponds to an approximate 3%–5% decrease in x-ray attenuation (23–25). In an animal model of MCA stroke, mean attenuation decreased from 50.0 to 48.4 HU at 1 hour and to 42.5 HU at 4 hours (21,22). Because these decreases in CT attenuation accompanying early stroke are small, their conspicuity may be increased at image review by using narrow window settings centered at approximately the mean attenuation in Hounsfield units of gray and white matter; the increase in lesion conspicuity achieved with this method can improve the accuracy of nonenhanced CT stroke detection.
The patients we examined do not represent a random population; diagnostically challenging cases were chosen for review specifically because their hypoattenuating ischemic regions were difficult to detect by using standard review settings. Thus, our reported sensitivity and specificity values were probably different from those that would be obtained from a prospective, consecutive patient population. Nevertheless, even in these patients with acute, difficult-to-detect stroke, we were able to achieve a sensitivity of approximately 70% by using nonstandard, variable soft-copy review settings. Even a small improvement in the diagnostic accuracy of stroke detection with CT could be important in the decision to perform thrombolytic treatment in a given patient.
Our standard window width and center level review settings were chosen empirically over time and represent a compromise necessary for the adequate hard-copy visualization of a variety of conditions including intra- and extraaxial hemorrhage, anterior and posterior fossa masses, and stroke. The idea of more accurately identifying hypoattenuating ischemic tissue, however, by taking advantage of subtle Hounsfield unit attenuation differences is not new. One group of researchers (34) has reported a postprocessing method for the CT detection of acute MCA-territory infarcts by using histogram analysis of attenuation values. By using their technique, the sensitivity for infarct detection was increased from the 61% for standard visual review to 96%. Unlike our method, however, attenuation difference analysis requires specialized postprocessing and additional interpretation time.
The use of interactively altered, soft-copy window width and center level settings did not significantly increase scan reading time from that required by using standard preset window width and center level settings. The two preset soft-copy review settings used for the interactive interpretations were typically close to what was required for optimal gray matter and white matter contrast. Our observations suggest that the extra time required to fine-tune these settings during image review was offset by the increased speed of diagnostic decision making resulting from increased lesion conspicuity, although these factors were not specifically measured.
The potential for inter- and intraobserver variability is an additional consideration in the emergency interpretation of stroke CT scans (15–19). The inter-observer variability reported in our study showed a moderately strong association, which is consistent with interobserver variability in other studies performed by highly trained readers (16). In a recent article (20) in the Journal of the American Medical Association, it was concluded that a group of 103 emergency physicians, neurologists, and general radiologists did not "uniformly achieve a level of sensitivity for identification of intracerebral hemorrhage sufficient to permit safe selection of candidates for thrombolytic therapy." Even brief periods of training, however, have been shown to increase diagnostic accuracy (15). Increased awareness of appropriate soft-copy CT scan review settings also has the potential to improve the ability of non–highly trained readers to detect the early changes of stroke.
In summary, we have demonstrated that the detection of acute ischemic brain parenchyma with nonenhanced CT scanning is facilitated by soft-copy visual review at a PACS workstation by using variable, nonstandard window width and center level settings. These review settings may be interactively optimized by the reader to accentuate the small attenuation difference between normal and acutely edematous brain tissue without an appreciable increase in the time required for image interpretation. Whether the early signs of infarction detected with such review can improve the prediction of hemorrhage risk and outcome in patients receiving thrombolytic therapy requires further study.
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Acknowledgments |
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Footnotes |
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Author contributions: Guarantors of integrity of entire study, R.G.G., J.F., M.H.L.; study concepts, R.G.G., W.J.K., G.J.H., J.F., M.H.L.; study design, M.H.L., J.F., R.G.G.; definition of intellectual content, R.G.G., W.J.K., G.J.H., J.F., M.H.L.; literature research, J.F., R.G.G., S.T.H., M.H.L.; clinical studies, M.H.L., J.F., J.J.G., S.T.H.; data acquisition, M.H.L., J.F., J.J.G., S.T.H.; data analysis, S.T.H., M.H.L., J.J.G.; statistical analysis, M.H.L., S.T.H.; manuscript preparation, M.H.L., S.T.H., J.F., R.G.G. manuscript editing and review, all authors.
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References |
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hours after a left inferior division MCA embolic stroke. Left: When reviewed at a PACS workstation by using standard virtual hard-copy settings (window width, 80 HU; center level, 20 HU), the left insular stroke is not definitely detectable. Right: With variable soft-copy settings (window width, 8 HU; center level, 32 HU) chosen to accentuate the gray matter and white matter interface, there is markedly increased conspicuity of the gray matter hypoattenuation at the left posterior putamen (arrow) and insular ribbon (arrowheads).
hours after left MCA stroke. (a) CT scans obtained with standard settings (window width, 80 HU; center level, 20 HU) show that the infarct is barely detectable as a minimal area of hypoattenuation of the left caudate head (arrows). (b) When reviewed by using variable soft-copy settings (window width, 8 HU; center level, 32 HU), the hypoattenuation of the gray and white matter of the left frontal operculum and of the left caudate head (arrows) demonstrate markedly increased conspicuity compared with the corresponding contralateral structures. (c) Follow-up nonenhanced CT scans at 33 hours after ictus show a large, superior-division left MCA infarction (arrows).
